Prognostic implication and functional exploration for microRNA-20a as a molecular biomarker of gastrointestinal cancer

Abstract

Background: It is generally accepted that microRNA-20a (miR-20a) is aberrantly expressed in gastrointestinal cancer (GIC), and may be associated with the prognosis of GIC patients. Nevertheless, the clinical prognostic value of miR-20a expression in GIC remains controversial.

Methods: We first conducted a comprehensive literature search of the clinical data and pooled them for evidence in assessing prognostic significance of miR-20a expression in GIC. Afterwards, we applied some bioinformatic analysis methods to explore the biological function of miR-20a and explain why miR-20a could act as an effective biomarker.

Results: The pooled results showed that enhanced miR-20a expression was significantly associated with poor survival in GIC patients (HR: 1.36; 95%CI: 1.21-1.52; P < 0.001). According to the subgroup analysis, the ethnicity, cancer type, sample source, and sample size may have an impact on the predictive roles for miR-20a. The gene ontologies enriched by the predicted miR-20a targets were highly associated with some important biological processes, cell components and molecular functions. Moreover, a series of prominent pathways linked with GIC carcinogenesis were identified. Ultimately, the crucial targets and modules were identified by constructing the protein-protein interaction network of miR-20a targets, which were highly associated with the initiation and progression of GIC according to previous molecular biology experiments.

Conclusions: Our results indicated that high expression of miR-20a may be a credible indicator of worse prognosis in GIC. Further studies involving biological experiments and larger sample sizes should be performed to validate these findings.

Keywords: Function exploration; Gastrointestinal cancer; Prognosis prediction; microRNA-20a.

Fig. 1

Flow diagram of filtering studies

Fig. 2

Forest plot of the relationship between miR-20a and overall survival in GIC. GIC, gastrointestinal cancer

Fig. 3

Sensitivity analysis for the pooled hazard ratios of overall survival of patients with high level of miR-20a expression. The sensitivity analysis was conducted to evaluate the stability of the pooled HR for OS by omitting one study at each step

Fig. 4

Top ten GO annotation results of miR-20a targets. a Biological processes (BP); b cell component (CC); c molecular function (MF). GO, gene ontology

Fig. 5

Pathway enrichment results. a Top 30 pathways enriched by all the targets of miR-20a; b Top 30 pathways enriched by the hub nodes of miR-20a. The Database for Annotation, Visualization and Integrated Discovery (DAVID version 6.8) online tool was applied to perform the pathway enrichment analysis

Fig. 6

The TGF-beta signaling pathway enriched in KEGG. Objects with pentagrams are acting locus by mapped genes. TGF-beta, Transforming growth factor-beta; KEGG, Kyoto encyclopedia of genes and genomes

Fig. 7

PPI network construction results. a Betweenness centrality distributions of nodes; b Closeness centrality distributions of nodes; c Degree distributions of nodes. PPI, protein-protein interaction

Fig. 8

The top three significant modules of the PPI network. The three modules were identified and reconstructed with Cytoscape. PPI, protein-protein interaction